Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection in adults and in young children. In the western world approximately all children have been infected by the age of two. In most cases the RSV infections will only cause minor upper respiratory illness with symptoms resembling that of the common cold. However, severe infection with the virus may result in bronchiolitis or pneumonia which may result in hospitalization or death. Infants who have been born prematurely or have a pre-existing lung disease are a high risk of severe infection and complications.
Respiratory syncytial virus (RSV) is a member of the order Mononegalirales, which consists of the non-segmented negative strand RNA viruses in the Families Paramyxoviridae, Rhabdoviridae and Filoviridae. RSV of humans (often termed RSV or HRSV) is a member of the Pneumovirus genus of the sub-family Pneumovirinae within the Family Paramyxoviridae. Other members of the Pneumovirus genus include viruses such as bovine RSV (BRSV), ovine RSV (ORSV) and murine pneumonia virus (MPV) amongst others. The sub-family Pneumovirinae also includes the genus Metapneumovirus which contains the recently identified and important human pathogen human metapneumovirus.
In addition to the genome features described above, Family characteristics include a lipid envelope containing one or more glycoprotein species considered to be associated with attachment and entry, of the host cell. Entry is considered to require a process by which the viral envelope fuses with the membrane of the host cell. Fusion of infected cells with, for example, their neighbours, can also result in the formation of fused multinucleate cells known as syncytia in some cases. The fusion process is believed to be glycoprotein mediated and is a feature shared with diverse enveloped viruses in other taxonomic groups. In the case of the Paramyxoviridae viruses of all genera characteristically express a fusion glycoprotein (F) which mediates membrane fusion
The only drug currently approved for the treatment of severe RSV is the antiviral medication, Virazole, also known as Ribavirin. This agent has a broad spectrum antiviral with virustatic effects, and acts by inhibiting RSV replication. It also improves arterial blood oxygenation. Unfortunately, the agent is toxic so that administration of the agent is confined to a hospital setting. Its administration is further complicated by the need to follow a strict procedural process when administering the agent in order to minimise the likelihood of certain adverse affects. The agent has a number of adverse effects including sudden deterioration of respiratory function (bronchiospasm). The efficacy of the agent has remained controversial and thus there is a real need to find an alternative agent for the treatment of RSV infection.
A number of agents are known to inhibit RSV. Published patent applications WO 01/95910 and WO 02/26228 (Bristol Myers Squib Company), the contents of which are incorporated by cross reference, describe a number of different types of compounds which exhibit anti-RSV activity in their description of the background art. Moreover, these applications describe compounds having antiviral activity against RSV of the formula

There are also a number of patent specifications that disclose imidazo-[2,1-a]-isoindole derivatives for uses other than treating RSV. U.S. Pat. No. 3,507,863 describes a number of polycyclic compounds that have anti-inflammatory and anti-convulsive activity. These compounds have the following general structure
where A is —NH—, —O— or —S—, and n is 1-3.
U.S. Pat. No. 3,770,766 describes polycyclic compounds that have antidepressant activity, and have the following general structure
where R3 is selected from various aromatic substituents.
U.S. Pat. No. 4,058,529 discloses anti-inflammatory and anti-convulsive activity polycyclic compounds of the general formula A, and includes compounds of the formula B where R2 is hydrogen or lower alkyl group (including amino substituted groups) and n is 1-3.

CH 482,697 (Graf) discloses a number of compounds of the general formula B above, where R2 is —CO—CHR—N3 and R is hydrogen or alkyl, and intermediates where R2 is —CO—CHR—NH2, —CO—CHR—OH or hydrogen. Likewise U.S. Pat. No. 3,590,043 (Graf) relates to compounds of the formula B where R2 is —CO—CHR—NR′R″. In this document n is 1 to 3, R is H or lower alkyl, R′ and R″ may be lower alkyl or benzyl or together form a piperidinyl or morpholinyl ring. The Graf compounds may have anti-inflammatory uses.
WO 02/066479 (Banyu Pharmaceutical) lists some compounds of the general formula B, where R2 is lower alkyl, —CO—C2H5 and selected other moieties. It also appears to suggest a compound of formula B where the fused phenyl ring has been replaced with pyridyl and R2 is methyl. It is not clear whether all of these compounds have been made. The compounds are for use in the treatment of high blood pressure and diabetes.
GB 1,038,735 discloses anti-inflammatory compounds of the general formula B, where n is 1 to 3, R2 is lower alkyl or, for example, an dimethylaminoethyl group.
Canadian patent application no. 2,108,899 (also see family member WO 92/16207) discloses various oxazolo-[2,3-a]-isoindole and imidazo-[2,1-a]-isoindole derivatives for use in antiviral medicaments, particularly for use in the treatment of AIDS and HIV. There are marked differences between HIV and RSV viruses, the diseases they are associated with, and the respective modes of action of the disclosed compounds. The specification generally describes compounds of the structure below where R is C1-C6 alkyl group or C1-C6 acyl group, and specifically discloses compounds where R is —COCH3 or —CH3.

A number of documents disclose compounds of the above formula or substituted forms thereof, where R is hydrogen. See for example the herbicidal compounds disclosed in U.S. Pat. Nos. 4,726,838 and 4,846,876.